1/116. The syndrome of carnitine deficiency.Three cases of lipid storage myopathy and carnitine deficiency are presented. Two had a fatal course and were insensitive to cortisone and carnitine-replacement therapy. The two fatal cases had lipid accumulation in organs other than the skeletal muscles and carnitine was reduced in plasma, skeletal muscles, heart and liver. fibroblasts from one of these "generalized" cases of carnitine deficiency were grown from a skin biopsy. Carnitine level, fatty acids uptake and oxidation were not appreciably different between the patients' fibroblasts and those of controls.- - - - - - - - - - ranking = 1keywords = storage (Clic here for more details about this article) |
2/116. Myopathy in very-long-chain acyl-coa dehydrogenase deficiency: clinical and biochemical differences with the fatal cardiac phenotype.A 30-year-old man suffered since the age of 13 years from exercise induced episodes of intense generalised muscle pain, weakness and myoglobinuria. fasting ketogenesis was low, while blood glucose remained normal. Muscle mitochondria failed to oxidise palmitoylcarnitine. Palmitoyl-CoA dehydrogenase was deficient in muscle and fibroblasts, consistent with deficiency of very-long-chain acyl-coa dehydrogenase (VLCAD). The gene of this enzyme had a homozygous deletion of three base pairs in exon 9, skipping lysine residue 238. fibroblasts oxidised myristate, palmitate and oleate at a rate of 129, 62 and 38% of controls. In contrast to patients with cardiac VLCAD deficiency, our patient had no lipid storage, a normal heart function, a higher rate of oleate oxidation in fibroblasts and normal free carnitine in plasma and fibroblasts. 31P-nuclear magnetic resonance spectroscopy of muscle showed a normal oxidative phosphorylation as assessed by phosphocreatine recovery, but a significant increase in pH and in Pi/ATP ratio.- - - - - - - - - - ranking = 1keywords = storage (Clic here for more details about this article) |
3/116. Infantile lipid storage myopathy with nocturnal hypoventilation shows abnormal low-affinity muscle carnitine uptake in vitro.An infant with respiratory insufficiency, cardiomyopathy, lipid storage myopathy and low muscle carnitine was diagnosed as having 'Ondine's curse' because of recurrent nocturnal hypoventilation. Carnitine uptake was studied in 20-day-old cultured muscle, where two distinct saturable transport components are recognized: the high- and low-affinity-uptake. Experimental evidence suggests that low-affinity-uptake is muscle-specific, operating at physiological carnitine concentration. In the patient's cultured myotubes, the low-affinity-uptake K(m) was 260% of controls (P < 0.01), whereas kinetic parameters of high-affinity uptake were normal. The high K(m) indicates an immature or altered carnitine muscle carrier, which may decrease the physiologic carnitine uptake.- - - - - - - - - - ranking = 5keywords = storage (Clic here for more details about this article) |
4/116. Early-onset fetal hydrops and muscle degeneration in siblings due to a novel variant of type IV glycogenosis.We report on 3 consecutive sib fetuses, presenting at 13, 12, and 13 weeks of gestation, respectively, with fetal hydrops, limb contractures, and akinesia. autopsy of the first fetus showed subcutaneous fluid collections and severe degeneration of skeletal muscle. Histologic studies demonstrated massive accumulation of diastase-resistant periodic acid-Schiff-positive material in the skeletal muscle cells and epidermal keratinocytes of all 3 fetuses. Enzyme studies of fibroblasts from the 3rd fetus showed deficient activity of glycogen brancher enzyme, indicating that this is a new, severe form of glycogenosis type IV with onset in the early second trimester.- - - - - - - - - - ranking = 7.3247571042257keywords = glycogen (Clic here for more details about this article) |
5/116. A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy.We have identified a novel missense mutation in the gene for glycogen branching enzyme (GBE 1) in a 16-month-old infant with a combination of hepatic and muscular features, an atypical clinical presentation of glycogenosis type IV (GSD IV). The patient was heterozygous for a G-to-A substitution at codon 524 (R524Q), changing an encoded arginine (CGA) to glutamine (CAA), while the GBE1 gene on the other allele was not expressed. This case broadens the spectrum of mutations in patients with GSD IV and confirms the clinical and molecular heterogeneity of this disease.- - - - - - - - - - ranking = 7.3247571042257keywords = glycogen (Clic here for more details about this article) |
6/116. riboflavin therapy. Biochemical heterogeneity in two adult lipid storage myopathies.Two unrelated adult males, aged 36 (patient 1) and 25 (patient 2) years, presented with subacute carnitine-deficient lipid storage myopathy that was totally and partly responsive to riboflavin supplementation in the two patients, respectively. plasma acyl-carnitine and urinary organic acid profiles indicated multiple acyl coenzyme a dehydrogenase deficiency, which was mild in patient 1 and severe in patient 2. The activities of short-chain and medium-chain acyl coenzyme A dehydrogenases in mitochondrial fractions were decreased, especially in patient 2. This was in agreement with Western blotting results. Flavin-dependent complexes I and II were studied by immunoblotting and densitometric quantification of two-dimensional electrophoresis with comparable results. Complex I was present in normal amounts in both patients, whereas complex II was decreased only in the pretherapy muscle of patient 2. Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) concentrations in muscle and isolated mitochondria, and the activity of mitochondrial FAD pyrophosphatase, showed that patient 1 had low levels of FAD (46%) and FMN (49%) in mitochondria, with a significant increase (P < 0.01) in mitochondrial FAD pyrophosphatase (273%) compared with controls. Patient 2 had similar low levels of FAD and FMN in both total muscle (FAD and FMN 22% of controls) and mitochondria (FAD 26%; FMN 16%) and normal activity of mitochondrial FAD pyrophosphatase. All of these biochemical parameters were either totally or partly corrected after riboflavin therapy.- - - - - - - - - - ranking = 5keywords = storage (Clic here for more details about this article) |
7/116. adult-onset acid maltase deficiency. Morphologic and biochemical abnormalities reproduced in in cultured muscle.We established muscle-tissue cultures from biopsy of a patient with adult-onset acid maltase deficiency. Morphologically and biochemically, the newly grown fibers of the cultured muscle showed the same abnormalities as those of the biopsied muscle. light microscopy showed multiple vacuoles filled with acid-phosphatase-positive material; on ultrastructural examination there was abnormal accumulation of glycogen in membrane-bound sacs (secondary lysosomes), some of which also contained dark membranous of homogeneous material. Acid maltase (pH 4.0), a lysosomal enzyme, was undetectable in either cultured or biopsied muscle by maltose hydrolysis, whereas acid phosphatase, also a lysosomal enzyme, was increased in both sources of muscle cells. Cultured muscle fibers demonstrate the same morphologic and biochemical abnormalities characteristic of biopsied muscle, supporting the concept of a biochemically distinct primary myopathy in man.- - - - - - - - - - ranking = 1.2207928507043keywords = glycogen (Clic here for more details about this article) |
8/116. Beta-enolase deficiency, a new metabolic myopathy of distal glycolysis.A severe muscle enolase deficiency, with 5% of residual activity, was detected in a 47-year-old man affected with exercise intolerance and myalgias. No rise of serum lactate was observed with the ischemic forearm exercise. Ultrastructural analysis showed focal sarcoplasmic accumulation of glycogen beta particles. The enzyme enolase catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate. In adult human muscle, over 90% of enolase activity is accounted for by the beta-enolase subunit, the protein product of the ENO3 gene. The beta-enolase protein was dramatically reduced in the muscle of our patient, by both immunohistochemistry and immunoblotting, while alpha-enolase was normally represented. The ENO3 gene of our patient carries two heterozygous missense mutations affecting highly conserved amino acid residues; a G467A transition changing a glycine residue at position 156 to aspartate, in close proximity to the catalytic site, and a G1121A transition changing a glycine to glutamate at position 374. These mutations were probably inherited as autosomal recessive traits since the mother was heterozygous for the G467A and a sister was heterozygous for the G1121A transition. Our data suggest that ENO3 mutations result in decreased stability of mutant beta-enolase. Muscle beta-enolase deficiency should be considered in the differential diagnosis of metabolic myopathies due to inherited defects of distal glycolysis.- - - - - - - - - - ranking = 1.2207928507043keywords = glycogen (Clic here for more details about this article) |
9/116. Infantile autophagic vacuolar myopathy is distinct from Danon disease.Lysosomal glycogen storage disease with normal acid maltase (Danon) is caused by primary lysosome-associated membrane protein-2 (LAMP-2) deficiency. Typically, the disease begins after the first decade; however, two infantile patients had similar histologic features. The infantile disorder is distinct from Danon disease, because, in both infants, LAMP-2 protein is present in skeletal muscle. Deposition of C5b-9 and multilayered basal lamina in one patient suggest that the infantile disease is pathogenically similar to X-linked myopathy with excessive autophagy.- - - - - - - - - - ranking = 12.358736897239keywords = glycogen storage disease, glycogen storage, storage disease, glycogen, storage (Clic here for more details about this article) |
10/116. Novel exon 11 skipping mutation in a patient with glycogen storage disease type IIId.We report the molecular genetic abnormalities of a patient with GSD IIId presenting with progressive myopathy and cardiopathy leading to a fatal outcome. We identified two independent deletions including a 4 bp deletion (117-1120) and a 98 bp deletion (1135-1232) in cDNA. Sequencing of the genomic dna of the corresponding region revealed a 4 bp deletion in exon 10; however, the other 98 bp deletion corresponding to exon 11, which was deleted in cDNA, was present in genomic dna. We therefore concluded that skipping of exon 11 occurred in the cDNA of the patient. Intron/exon boundary analysis of the skipped exon 11 revealed no mutation in the consensus splice-site sequence. If normal splicing had occurred, a stop codon would have appeared within exon II due to frameshift mutation. The mechanism of exon skipping observed in our patient is as yet unknown, and it is still not clear whether intraexonal mutation of the preceding exon can influence splice-site selection. It is possible that a unique exon skipping occurred, preventing the appearance of a stop codon in our patient.- - - - - - - - - - ranking = 78.739482536425keywords = glycogen storage disease, glycogen storage disease type, glycogen storage, storage disease, storage disease type, glycogen, storage, disease type (Clic here for more details about this article) |
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